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JONSSON COMPREHENSIVE CANCER CENTER AT UCLA IS USING A NEW EXPERIMENTAL THERAPY FOR METASTATIC BREAST CANCER
The theory is simple. The practice is complex. The effort is to render harmless certain cancerous tumors. Dr. Mai Nguyen is combining theory, practice and effort at the Jonsson Comprehensive Cancer Center at UCLA, where she is in charge of the only site in the country where breast cancer is being treated with the experimental drug TNP-470.
Nguyen noted that cancer tumors require blood supplies for nourishment. Also, blood acts as a vehicle for carrying cancerous cells from tumors to other organs; that's one way cancer spreads to different parts of the body. "TNP-470 prevents the formation of minute blood vessels called capillaries," Nguyen said. "Normally in adults with cancer, the only new capillaries that form are in the tumor beds."
By preventing the formation of capillaries in tumors of metastatic breast cancer patients, Nguyen hopes to cut off the tumors' blood supplies, thereby causing the tumors to shrink to a harmless size and precluding the spread of cancer from those tumors.
"What I am doing in my study at UCLA is ascertaining the safety of TNP-470 and determining whether or not the drug is as effective as we believe it to be," Nguyen said. "Patients in my study must have metastatic breast cancer; that is, the cancer must have spread from the breast to at least one other part of the body. They must have undergone chemotherapy that either stabilized or shrank their tumors," said Nguyen, who is an assistant professor at the UCLA School of Medicine.
In Nguyen's study, two-thirds of the patients receive intravenous infusions of TNP-470, while the remaining one-third are given a placebo.
"Laboratory tests have shown that when tumors are deprived of their blood supplies by TNP-470, the tumors shrink to a harmless size of about one millimeter. They stay that size as long as TNP-470 is administered three times a week. And those tests further indicate that, since the tumors have no blood supply, they don't spread," Nguyen said.
Currently, TNP-470 is given intravenously, but researchers are working to develop an oral formula.
Side effects of TNP-470 are minimal, Nguyen said. She noted that with doses 18 percent higher than those she is using, patients complained of fatigue, nausea, dizziness and depression, but she said she hopes the dose sizes she will be using will minimize those side effects.
Nguyen graduated from Harvard Medical School, where she studied with Dr. Judah Folkman, a pioneer in the field of angiogenesis, which deals with the formation of blood vessels. TNP-470 is an angiogenesis inhibitor.
"Dr. Nguyen was one of our most outstanding postdoctoral fellows, and she is a superb surgeon," Folkman said."She developed a novel method to test the efficacy and potency of angiogenesis inhibitors in a very quantitative way. Previously, there had been no such quantitative method. I am not surprised to hear of her success at UCLA."
It was Dr. Donald Ingber, then a postdoctoral fellow in Folkman's lab, who discovered the substance that led to the development of TNP-470. That discovery began with an accident, when some cells in a laboratory culture became infected with a fungus. They were endothelial cells, which are cells that line blood vessels. Ingber, who is now an associate professor at Harvard Medical School, noted that the infected cells were not growing as well as the healthy cells in the culture.
Folkman and Ingber isolated the ingredient of the fungus that was inhibiting growth of the blood vessel cells, and together with the Japanese company Takeda Chemical Industries, they developed TNP-470 based on that ingredient.
Patients accepted in the TNP-470 study after an initial examination at UCLA will receive intravenous infusions of the drug or a placebo three times a week for three months, Nguyen said. Persons interested in learning whether they qualify to participate in the study should call Nguyen at (310) 206-2215